This research program proposes to study the biochemical and neurochemical basis of alcohol drinking behavior in genetically-selected inbred strains of rats which exhibit natural alcohol preference (P) and aversion (nonpreference, NP) and to develop the P-strain as an animal model for alcoholism. The following correlates of alcohol preference and nonpreference will be sought by comparison of the P and NP strains: 1) innate differences in brain alcohol and acetaldehyde metabolism, alcohol and aldehyde dehydrogenase activity, (Na ion-K ion)-ATPase activity and the steady-state level and metabolism of serotonin, norepinephrine and dopamine. The brain contents of acetylcholine, taurine, gamma-aminobutyric acid and other putative amino acid neurotransmitters will also be measured. 2) differences in the acute and chronic effects of ethanol administration on brain (Na ion-K ion)-ATPase, calcium and the content and metabolism of neurotransmitter compounds. The contribution of natural and conditioned taste aversion to the drinking behavior of the NP strain will also be sought. The natural alcohol preference behavior of the P-strains will be maximized by techniques such as the use of sweeteners, food-restriction and total darkness in order to attain states of prolonged intoxication, dependence and withdrawal.